1. Acta Derm Venereol 2011; 91: 44–49
CLINICAL REPORT
Tolerability and Safety of Biological Therapies for Psoriasis in Daily
Clinical Practice: A Study of 103 Italian Patients
Alexandra Maria Giovanna BrUNASSo1,2, Matteo PUNToNI3, Camilla SALVINI4, Chiara DElFiNo5, Pero CUrCIC6, Andrea
GULIA7 and Cesare MASSoNE6
Departments of 1Environmental Dermatology and Venereology, 6Dermatology, Medical University of Graz, Graz, Austria, Departments of 2Dermatology,
3
Oncology and Biostatistical Research, Galliera Hospital, Genoa, 4Department of Dermatology, Prato Hospital, Prato, 5Department of Dermatological
Sciences, University of Florence Medical School, Florence, and 7Department of Dermatology, University of L’Aquila, L’Aquila, Italy
Studies comparing the safety and tolerability of biologi- period of time (12–24 weeks) (4–10); however, there is
cal therapies for psoriasis in the long-term and in daily a lack of direct comparison of the tolerability and safety
clinical practice are lacking. Most published studies are of different biological agents with long-term follow-up,
of selected patients with short-term (3–6 months) follow- and of reports of experience of the daily management
up. We performed a retrospective cohort study of 103 pa- of unselected patients with psoriasis (i.e. reflecting the
tients in order to describe the frequency and the clinical clinical experience of dermatologists).
features of adverse events, and to evaluate and compare
the tolerability and safety of efalizumab, etanercept, in-
fliximab, and adalimumab in clinical practice. A total of METhoDS
136 courses of biological therapies were administered, Objectives
with a mean duration of 16 months/patient; 55 patients
A retrospective cohort study was carried out, which aimed to
received efalizumab, 45 etanercept, 33 infliximab, and describe the frequency and clinical features of adverse events
3 adalimumab. Infliximab had an incidence rate ratio in a cohort of patients with psoriasis and psoriatic arthritis
of suspension due to severe adverse events 5.9 times who underwent biological therapies from May 2003 to April
(95% confidence interval (95% CI) 1.9–18, p < 0.001) 2009, and to evaluate and compare the tolerability and safety
higher than etanercept and 9.8 times (95% CI 3.2–30.1, of biological therapies.
p < 0.001) higher than efalizumab. Safety profiles for efa-
lizumab and etanercept were more favourable than for Participants
infliximab. Concerning tolerability, we found that more Case files of 103 patients were reviewed (male:female ratio 64:39,
patients responded to infliximab, but long-term tolerabi- mean age 51.4 years, median age 52 years, age range 14–81 years)
lity was higher for both efalizumab and etanercept due followed in the outpatient psoriasis clinics of Florence University
(91 patients) and Genoa Galliera Hospital (12 patients) who under-
to the better safety profile and a higher compliance to went biological therapies during the period May 2003 to April
therapy. Key words: psoriasis; adverse events; efalizumab; 2009. Clinical charts were reviewed for demographics, psoriasis
etanercept; infliximab; adalimumab; tolerability; safety. characteristics and severity (Psoriasis Area Severity Index (PASI),
static physicians global assessment (s-PGA), dermatology life
(Accepted May 18, 2010.) quality index (DLQI)), joint involvement, previous dermatological
treatments, biological treatment followed (duration, dosages and
Acta Derm Venereol 2011; 91: 44–49. adverse events) and concomitant systemic psoriatic treatments
(duration and dosages). Patients were visited by the same derma-
Cesare Massone, Department of Dermatology, Medical tologist monthly for the first 3 months, then at 2-month intervals.
University of Graz, Auenbruggerplatz 8, AT-8036 Graz, Before treatment initiation, complete blood cell count and routine
Austria. E-mail: cesare.massone@klinikum-graz.at biochemical analysis were performed, including testing for hepa-
titis B and C markers, antinuclear antibodies (ANA), anti-DNA
antibodies, chest X-rays, and Mantoux test. CBC and routine
biochemistry were performed monthly for the first 3 months
Psoriasis is a common inflammatory skin condition with and then at 2-month intervals during the treatment period. Chest
an estimated incidence of 2–3% in Europa and North X-rays and Mantoux test were performed yearly and ANA and
America (1). High-need patients, defined as psoriasis anti-DNA antibodies every 6 months.
subjects with a moderate to severe condition who have
failed to respond to two systemic conventional therapies Description of procedures
due to lack of efficacy, intolerance or contraindication, are Adverse events (AE) were classified as mild (MAE: did not
eligible to receive biological therapies (2, 3). Since the required treatment suspension) or severe (SAE: required therapy
approval of biological therapies, concerns about safety suspension and/or close monitoring and/or additional systemic
therapy and those that resulted in persistent or significant disa-
have been raised. Efficacy and safety have been evaluated bility or those that were life-threatening).
in many clinical trials conducted on selected patients Flare was defined as typical or unusual worsening of disease
with a single biological agent, most of them for a short during treatment and/or occurrence or new psoriasis morpho-
Acta Derm Venereol 91 © 2011 The Authors. doi: 10.2340/00015555-0959
Journal Compilation © 2011 Acta Dermato-Venereologica. ISSN 0001-5555

2. Tolerability and safety of biological therapies for psoriasis 45
logies (11). Switch of psoriasis morphology was defined as the to the expected number of cancers for biological therapy.
emergence of a new type of psoriasis (12). Generalized inflam- Ninety-five percent confidence intervals (95% CIs) for the
matory flare (GiF) was defined as the presence of widespread, SiRs were calculated based on the Poisson analysis (13). The
erythematous, oedematous lesions involving existing plaques. expected numbers of cancers for SiR calculations were based
immunogenicity was defined as the detection of positive on the regional Tuscany Cancer registry, data source: 5-year
autoantibodies in patients whose baseline autoimmunity status age-specific cancer incidence rates obtained from the database
was confirmed as negative (measured by ANAs and ds-DNA (2002 to 2006) for all cancers.
antibodies).
Safety and tolerability. Safety assessment was based on the rate
of adverse events and the rate of withdrawals due to SAE. rESULTS
Tolerability assessment was based on the long-term adherence to
therapy inversely measured by the overall rate of withdrawals. A total of 75 patients were affected by psoriasis and 28
Efficacy was measured as a secondary end-point in order to patients were affected by both psoriasis and psoriatic
compare adherence to therapy and to assess tolerability. In
terms of efficacy, patients were classified into two groups: (i)
arthritis (confirmed by rheumatologist consultation in
responders and (ii) non-responders; a further quantification of all cases). Patients were followed for an average of 39
the level of response was beyond the scope of this research. months (range 1–72 months). The mean number of sys-
Responders were defined as subjects who achieved a PASi-50 temic therapies (acitretin, cyclosporine, methotrexate,
response (50% improvement compared with baseline-PASi) psoralen plus ultraviolet A (PUVA) and fumaric esters)
or an sPGA score of mild, minimal or clear, or patients who
benefited from a quality of life improvement (measured by the
used in the past was 3.4 (range 1–5, median 3). A total of
DlQi) superior to 50% measured at week-12. Non-responders 136 courses of biological therapies were administered,
or lack of efficacy were defined as patients who did not achieve with a mean duration of 16 months/patient. Fifty-five
a PASI-50 response or an sPGA score of mild, minimal or clear, patients (40%) received efalizumab, 45 (33%) received
or patients who did not benefit from a 50% improvement in etanercept, 33 (24%) received infliximab, and 3 (2%)
quality of life (measured by the DlQi) within a time period of
at least 12 weeks.
received adalimumab. Twenty-six patients (25%) re-
Loss of response was defined as a loss ≥ 25% of the best PASi ceived more than one biological therapy, though not
or the best sPGA or the best DLQI values obtained during treat- concomitantly (7 patients (7%) received three and 19
ment, measured after the initial 12 weeks of response. patients (18%) received two biologicals, respectively).
Twenty-nine patients (28%) received an additional
Statistical methods therapy cycle (re-treatment) after suspension with eta-
Standard descriptive statistics, such as mean, median and
nercept (25 patients) and efalizumab (4 patients). The
standard deviations were computed for continuous variables, duration and schedule of each treatment are reported in
and rounded numbers (%,) were used for categorical variables. Table i. No statistically significant differences in age,
Differences in body weight from day 0 to month 6 within groups sex and associated comorbidities were present between
were compared with the Wilcoxon’s signed rank sum test using treatment groups. Some differences in the percentage of
Statistical Package for Social Sciences (SPSS) version 12.0
software. All p-values are two-sided and p < 0.05 was considered
patients naïve for biological therapies were noted (in-
statistically significant. Poisson regression models using Stata, fliximab 94% vs. efalizumab 75% and etanercept 65%)
version 10.0 software (Stata-Corp lP, College Station, TX, (Table i). Being a retrospective study, our patients were
USA) were used to estimate the incidence rate ratio (iRR) of treated according the knowledge and the drugs available
SAE, of withdrawals due to SAE and to compare the efficacy, at that time: 28 patients affected by psoriatic arthritis
tolerability and safety between the different biological therapies.
Data for each biological therapy were analysed separately.
received only anti-tumour necrosis factor (TNF)-α
For the comparison between malignancy data vs. the gene- agents (in 2003 infliximab was the only drug available
ral population data, standardized incidence rates (SiRs) were in our service, in 2004 we started to use etanercept and
calculated using the ratio of the observed number of cancers in 2008 adalimumab). In 2005, our patients affected only
Table I. Patient numbers (% naïve to biological agents), treatment durations and schedules
Efalizumab Etanercept infliximab Adalimumab
Patients, n 55 45 33 3
Naïve, % 75 64 95 0
Treatment duration (months)
Mean 19.4 17.8 8.7 18.7
Median 12.5 13 8 –
range 2–46 3–42 1–31 9–34
Dosing Single conditioning dose of 0.7 50 mg s.c. 2/week for 12 weeks, Intravenous infusions of 5 80 mg at day 0 followed by
mg/kg s.c., followed by 1 mg/kg followed by 25 mg s.c. 2/week or 50 mg/kg/day at week 0, 2, 6 40 mg every other week, from
weekly. Suspended in February mg s.c. 1/week for other 12 weeks and every 8 weeks thereafter. week 1 to discontinuation.
2009 in all 29 patients under until week 24 for psoriasis patients Premedication with
treatment according to EMEA and uninterrupted for psoriatic intravenous antihistamine
recommendation (14). arthritis. EMEA protocol. and hydrocortisone.
EMEA: European Medicines Agency; s.c.: subcutaneously.
Acta Derm Venereol 91

3. 46 A. M. G. Brunasso et al.
Table II. Monthly incidence rates of adverse events and with- 1.8 times (95% CI 0.9–3.5, p = 0.1) higher than efalizu-
drawals mab, with a non-statistical significant difference.
Patients Monthly incidence Table III reports MAE observed in our cohort of
n rate, % patients. Weight gain was evaluated in patients treated
Efalizumab for at least 6 months with every single biological agent.
Withdrawal (any reason) 26 2.44 Differences in body weight increment were signifi-
Withdrawal (adverse events) 5 0.47 cantly higher among etanercept- and infliximab-treated
Adverse events (any) 63 5.92
Serious adverse events 16 0.83
patients compared with efalizumab-treated patients
Etanercept (p < 0.001). The relative risk of gaining body weight
Withdrawal (any reason) 26 2.91 among patients exposed to etanercept or infliximab
Withdrawal (adverse events) 5 0.62 was 14 times higher than in patients exposed to efali-
Adverse events (any) 40 4.99 zumab (95% CI 3.14–62.46, p < 0.001). No significant
Serious adverse events 17 0.95
difference in body weight gain was observed between
Infliximab
Withdrawal (any reason) 29 10.1 etanercept- and infliximab-treated patients (p = 0.1).
Withdrawal (adverse events) 8 2.77 Table iV shows the SAE observed in our cohort of
Adverse events (any) 20 6.97 patients. The incidence of neoplasia in our cohort of
Serious adverse events 16 1.83
patients vs. the general population was not significantly
Adalimumab
Withdrawal (any reason) 3 0.32
greater than 1; SIrs (95% CI) for colon carcinoma 7.13
Withdrawal (adverse events) 2 0 (0.18–39.73), hepatic carcinoma 35.10 (0.89–195.49),
Adverse events (any) 0 0.16 and lung carcinoma 5.92 (0.72–21.37).
Serious adverse events 1 0 Haematological events. As already reported by our
group, 4 (5%) of 81 patients who received anti-TNF-α
by moderate to severe plaque psoriasis were eligible to agents developed drug-induced thrombocytopaenia
receive efalizumab until February 2009, when all 29 during treatment (15, 16).
patients suspended treatment according to the European Infusion reactions. interruption of therapy was requi-
Medicines Agency (EMEA) recommendation (14). red in 2 infliximab patients (6%). All the patients who
In April 2009, 19 (42%) etanercept-treated patients, experienced infusion reactions were not following
4 (12%) infliximab-treated patients and one (33%) concomitant immunomodulatory therapy.
adalimumab-treated patient were continuing therapy. Arthritis-related adverse events. In our cohort of 1,058
Twenty-three (65%) infliximab-treated patients recei- patient-months treated with efalizumab, the frequency
ved concomitant therapy with methotrexate (5–10 mg/ of confirmed psoriatic arthritis onset was 22.7 per 1,000
week) from baseline for the whole period of infusions. patient-years.
In 3 (6%) efalizumab-treated patients cyclosporine th- Immunogenicity. Seven patients (21%) developed po-
erapy at 3 mg/kg/day was added in order to control an sitive ANA titres (superior to 1/160) during infliximab
inflammatory flare. No concomitant systemic therapy therapy (6 patients were taking infliximab as monother-
was followed in patients receiving etanercept and ada- apy and 1 patient was under concomitant methotrexate
limumab. therapy) without other criteria for drug-induced lupus.
in two patients the development of human anti-chimeric
Adverse events antibodies (HACAs) was confirmed by the radioimmu-
noassay detection method (antigen-binding assay).
Table II details the monthly incidence rates of adverse
events. infliximab had an incidence rate ratio (iRR) of Tolerability and efficacy
SAE 3.5 times (95% CI 1.8–6.9, p < 0.01) higher than
etanercept and 6.2 times (95% CI 3.2–30, p < 0.001) Table V reports in detail the reasons for withdrawal or
higher than efalizumab. Etanercept had an Irr of SAE suspension of therapy. Eighteen patients (17%) sus-
Table III. Mild adverse events observed in our patients
Efalizumab Etanercept infliximab Adalimumab
influenza-like symptomsa, n (%) 42 (76) 2 (4) 2 (6) 1 (33)
Injections site reactionsb, n (%) 2 (4) 22 (49) 0 0
Mild infections, n (%) 1 (2)c 1 (2)d 1 (3)e 0
Weight gainf, n (%) 3 (4) 19 (42) 11 (32) 0
Weight gain (kg), mean ± SD 0.13 ± 0.76 (p = 0.2) 1.51 ± 1.95 (p < 0.001) 0.93 ± 1.565 (p = 0.007) Not evaluated
observed within 48 h after the infusion. bDefined as local erythema, itching, burning, pain, oedema or urticaria. c4 episodes of herpes genitalis.
a
d
Bronchitis. eherpes zoster. fEvaluated only in patients treated for at least 6 months.
SD: standard deviation.
Acta Derm Venereol 91

4. Tolerability and safety of biological therapies for psoriasis 47
Table IV. Severe adverse events observed in our patients
Efalizumab Etanercept infliximab Adalimumab
n (%) n (%) n (%) n (%)
Serious infections 0 1a (2) 1b (3) 0
Skin malignancies 2c (4) 0 0 0
Invasive malignancies 2d (4) 1e (2) 1f (3) 0
Congestive heart failure 0 0 0 0
Thrombocytopaenia 0 2 (4) 2 (6) 0
Aplastic anaemia or pancitopaenia 0 0 0 0
Neurological events 1g (2) 0 0 0
Infusion reactions 0 0 4 (12) 0
Arthritis-related adverse events 2h (4) 0 1i (3) 0
Immunogenicity 0 2j (4) 7k (21) 0
Psoriasis flares
Transient localized papular eruptions 2l (4) 0 0 0
Switch of psoriasis morphology 4m (7) 1n (2) 0 0
Generalized inflammatory flare 3o (6) 0 0 0
a
Disseminated tuberculosis. brecurrent herpes zoster (4 episodes). cone basal cell carcinoma and one in situ melanoma. dTwo cases of lung carcinoma
after 16 and 20 weeks of therapy, in two heavy smokers. eone case of colon carcinoma after 23 months of therapy. fone case of hepatic carcinoma after
21 months of infliximab + methotrexate. gone case of aseptic meningitis. hConfirmed psoriatic arthritis after 31 and 56 weeks of therapy. iGeneralized
arthralgia in the context of drug-induced lupus erythematosus (see immunogenicity). jone patient was affected by autoimmune thrombocytopaenia. kone
patient developed drug-induced lupus erythematosus, which completely regressed after 6 months from withdrawal and prednisone therapy. Another patient
developed autoimmune thrombocytopaenia. lBetween the 10th and 15th weeks of therapy. monset of plaque face psoriasis in two cases and generalized
pustular psoriasis in two cases. nonset of palmoplantar pustular psoriasis after 12 months of therapy. ooccurred in 3 responders (after 10 weeks, 21 months
and 19 months of uninterrupted therapy) not triggered by infections. The GiF was managed successfully in all of the patients without discontinuing
efalizumab with a short course of cyclosporine at 3 mg/kg/day, and tapered off once symptoms were under control.
pended therapy due to SAE. Withdrawals were highest efalizumab (95% CI 2.6–6.4, p < 0.001); etanercept was 1.2
between infliximab-treated patients, mainly due to SAE times more efficacious than efalizumab (95% Ci 0.8–1.9,
as infusion reactions (6%), immunogenicity (21%) and p = 0.4) but the difference is not statistically significant.
lack of adherence to therapy (21%). Lack of efficacy/ The small sample size of adalimumab-treated patients
non-responders was the main reason of withdrawal from makes it impossible to compare efficacy, incidence of
efalizumab (13%) and from etanercept (22%). Loss of SAE and incidence of suspension due to SAE with the
response was the most frequent reason for withdrawal other biological therapies.
from adalimumab therapy (67%). in 2 (6%) infliximab- Re-treatment. No loss of efficacy was seen during re-
methotrexate-treated patients the clinical response was treatment with efalizumab (4 patients) or etanercept (25
diminished, because the interval of response was shorte- patients).
ned after 22 weeks and 38 weeks of interrupted therapy
and infusions were continued at 6-week intervals.
infliximab had an iRR of suspension due to SAE 5.9 DISCUSSIoN
times (95% CI 1.9–18, p < 0.001) higher than etanercept high-need psoriasis patients require long-term treatment
and 9.8 times (95% CI 3.2–30.1, p < 0.001) higher than plans where stable efficacy, safe profile and compliance
efalizumab. Etanercept had an Irr of suspension due to became essential. Unfortunately, most clinical research
SAE 1.7 times (95% CI 0.5–5.8, p = 0.4) higher than efa- worldwide in psoriasis consists in short-term (3–6
lizumab with a non-statistical significant difference. months) evaluations in selected patients (4–10, 17, 18).
infliximab was 3.4 times (95% Ci 2.1–5.5, p < 0.001) our study is an attempt to compare the tolerability and
more efficacious (in terms of responders vs. non respon- safety of efalizumab, etanercept and infliximab in daily
ders) than etanercept and 4.1 times more efficacious than clinical practice and for a long follow-up period. in
addition a few patients treated with adalimumab were
Table V. Reasons for withdrawal or suspension of therapy studied. The mean follow-up of our patients (39 months)
and the mean treatment duration (16 months/patient)
Efalizumab Etanercept infliximab Adalimumab are the longest to our knowledge found in the literature
n (%) n (%) n (%) n (%) (4–10, 17, 18).
SAE 5 (9) 5 (11) 8 (24) 0 The majority of papers published to date, assess the
lack of efficacy 7 (13) 10 (22) 1 (3) 0
Loss of response 1 (2) 4 (9) 6 (18) 2 (67)
efficacy and safety of single drugs in selected cohorts
lost in follow-up 7 (13) 7 (16) 7 (21) 0 of patients; long-term randomized controlled trials that
Patient request/other 1a (2) 1b (2) 7 (21) 0 compare the efficacy, tolerability and safety of different
a
Alcoholism.bPregnancy. biologicals are lacking and only one study, by Warren
SAE: serious adverse events. et al. (4), compares the efficacy and safety of different
Acta Derm Venereol 91

5. 48 A. M. G. Brunasso et al.
biologicals, but without analysing tolerability and ad- dering the low number of adalimumab-treated patients,
herence to therapy (5–10, 17, 18). the proportion 1:104 is mis-estimated. Loss of response
in our patients the safety profiles of efalizumab and was the cause of withdrawal in a higher percentage of
etanercept were more favourable than the safety profile patients during adalimumab therapy (67%) compared
of infliximab. in fact, in Europa and North America in- with efalizumab (2%), etanercept (9%) and infliximab
fliximab had an iRR of SAE 3.5 times (p < 0.01) higher (18%) therapy. No loss of response during infliximab
than etanercept and 6.2 times (p < 0.001) higher than efa- treatment was seen in patients treated concomitantly
lizumab. infliximab frequently causes infusion reactions with methotrexate, but the clinical response was shor-
and immunogenicity, whereas injection site reactions tened in two cases. We hypothesize that the loss of
should be considered for etanercept and influenza-like response seen during infliximab treatment could be
symptoms for efalizumab. Since efalizumab is no longer associated with the rapid clearance of infliximab due
commercially available the most relevant comparisons to the development of antibodies (hACAs) in patients
can be made between etanercept and infliximab. immu- not following concomitant immunomodulatory therapy,
nomodulatory therapy (methotrexate) associated with even if HACAs were not measured in this group of
infliximab reduced the frequency of infusion reactions patients (19).
and immunogenicity (19), improving tolerability. Weight A systematic review and meta-analysis by Schmitt
gain was significantly higher among etanercept- and et al. (24) regarding efficacy and tolerability of syste-
infliximab-treated patients compared with efalizumab- mic treatments for psoriasis concluded that there is a
treated patients, in accordance with previous literature significant difference in efficacy between biologicals;
reports (20). Drug-induced thrombocytopaenia was more infliximab being the most efficacious, followed by
frequent during etanercept and infliximab treatment, the- adalimumab. our data confirm indirectly the efficacy
refore immediate monitoring of platelet count is recom- outcome of this meta-analysis, despite the fact that in
mended and autoimmunity should be suspected (15, 16). our study efficacy was measured only secondarily in
The overall risk of carcinoma was not increased during order to assess tolerability. our experience differs in the
the course of treatment with biologicals when compared safety results: we found a higher monthly incidence of
with the general population, as confirmed by different withdrawals due to SAE for infliximab (2.77% vs. 1.3%)
published trials (17, 18). We noticed a higher frequency and a lower incidence for efalizumab (0.47% vs 1.2%)
of efalizumab-associated arthritis events; considering the and etanercept (0.62% vs. 1%). Possible explanations
worldwide reported efalizumab post-marketing surveil- may reside in our smaller cohort size, the unselected
lance frequency of arthopathies of 4.8 per 1,000 patient- type of patients and the different follow-up time. Con-
years, our findings (22.7 per 1,000 patient-years) may cerning tolerability, Schmitt et al. (24) reported similar
be over-estimated due to the small sample size (21). In overall rates of adverse events and withdrawals between
February 2009, EMEA recommended the suspension of infliximab, etanercept, efalizumab and adalimumab,
marketing authorization for efalizumab due to safety con- but direct comparison between different biologicals
cerns, including the occurrence of progressive multifocal was not reported, due to the differences in the duration
leukoencephalopathy (14); except for one event (aseptic of individual trials and the lack of key comparative
meningitis), no other neurological events were observed data concerning long-term safety. In our experience,
in our efalizumab-treated patients. The frequencies of efalizumab and etanercept appear to be better tolerated
psoriasis flares in our patients are in accordance with than infliximab (24).
reports in the literature (22, 23). GiF has been described Warren et al. (4) conducted a case-note review of 102
in non-responding efalizumab-treated patients during the psoriasis patients treated with infliximab, etanercept and
first weeks of treatment and after withdrawal; however, efalizumab to assess efficacy and safety in the clinical
we reported a 6% frequency not associated with the initial setting. These authors reported that all three biologicals
phases of therapy or with discontinuation (23). were well tolerated, but direct comparison of tolerabi-
Concerning tolerability, we found that more patients lity rates was not performed (4). liver abnormalities
responded to infliximab, but long-term tolerability was were reported in 7–20% of patients, suggesting a drug-
higher for both efalizumab and etanercept due to the induced liver hepatotoxicity susceptibility in psoriasis
better safety profile and higher compliance with therapy, patients (4). These findings were not encountered in our
which may be related to the more convenient route of cohort of patients, perhaps due to different alcohol con-
administration. sumption rates between our populations. Unfortunately,
The monthly proportion of patients that continued to date we cannot compare our tolerability rates with
therapy against the monthly withdrawals favoured other similar studies because reports of direct compa-
efalizumab (one monthly withdrawal for every 23.6 pa- rison between biological agents are lacking.
tients) and etanercept (1 monthly withdrawal for every Being a retrospective study, this work was prone to
14.5 patients) and was not encouraging for infliximab selection biases; although no statistically significant
(1 monthly withdrawal for every 1.2 patients). Consi- differences in age, sex and associated co-morbidities
Acta Derm Venereol 91

6. Tolerability and safety of biological therapies for psoriasis 49
were present between treatment groups, differences in 10. Antoni CE, Kavanaugh A, van der heijde D, Beutler A,
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ACkNoWlEDGEMENTS (efalizumab). Available from: http://www.emea.europa.eu/
We are indebted to Dr Emanuele Crocetti who provided us the humandocs/PDF/EPAR/raptiva/ 2085709e.
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The authors declare no conflict of interest. psoriasis. J Am Acad Dermatol 2009; 60: 781–785.
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